Exploring Genetic Variants and Platinum Chemotherapy Response in Indonesian Non-Small Cell Lung Cancer Patients: Insights from ERCC2 rs13181

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2024-09-20 DOI:10.2147/ott.s475219

Nadiya Nurul Afifah, Lanny Indah Permatasari, Ajeng Diantini, Ruri Intania, Indra Wijaya, Hideru Obinata, Melisa Intan Barliana

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引用次数: 0

Abstract

Purpose: Individual responses to platinum-based treatment for Non-Small Cell Lung Cancer (NSCLC) are influenced by genetic polymorphisms, including Single Nucleotide Polymorphisms (SNPs). This study aimed to explore the role of ERCC2 in the Nucleotide Excision Repair (NER) pathway for platinum-based chemotherapy in NSCLC. While ERCC2 is widely studied, data for Southeast Asian populations are lacking. Addressing this gap could improve personalized treatment strategies for NSCLC in this demographic.
Patients and Methods: This study recruited 82 NSCLC patients with wildtype mutations of EGFR at Dr. H.A. Rotinsulu Lung Hospital, Bandung, and Dharmais Cancer Hospital, Jakarta. Data were collected prospectively from whole blood samples and medical records, while the effectiveness of chemotherapy was assessed by evaluating the response using RECIST 1.1 criteria on fourth cycle of chemotherapy.
Results: The results of this study showed the presence of genotype variation among the subjects, with frequency distribution as follows: AA genotype (82.9%), AC genotype (15.9%), and CC genotype (1.2%). The analysis of the association between ERCC2 rs13181 CC + AC versus AA with RECIST 1.1 yielded an odds ratio (OR) of 1.042 (95% CI: 0.292– 3.715; p=0.950). A multivariate analysis that included cancer stage and chemotherapy regimen as additional variables produced an adjusted odds ratio (aOR) of 0.970 (95% CI: 0.263– 3.568; p=0.963).
Conclusion: This study did not find statistically significant associations between ERCC2 rs13181 polymorphisms and chemotherapy responses. However, this research highlights the presence of genetic variation within the Indonesian population, with the AA genotype being the most prevalent, which may influence chemotherapy responses. The results provided preliminary data and lay the foundation for future comprehensive cohort observational investigations.

Keywords: ERCC2, genetic polymorphism, Indonesia, RECIST 1.1, platinum-based

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探索印度尼西亚非小细胞肺癌患者的遗传变异与铂类化疗反应：从 ERCC2 rs13181 中得到的启示

目的：非小细胞肺癌（NSCLC）铂类治疗的个体反应受遗传多态性（包括单核苷酸多态性（SNP））的影响。本研究旨在探讨ERCC2在NSCLC铂类化疗的核苷酸切除修复（NER）途径中的作用。虽然ERCC2已被广泛研究，但东南亚人群的数据却很缺乏。填补这一空白可以改善这一人群的NSCLC个性化治疗策略：本研究在万隆H.A. Rotinsulu肺病医院和雅加达Dharmais癌症医院招募了82名表皮生长因子受体野生型突变的NSCLC患者。数据通过全血样本和病历进行前瞻性收集，化疗效果则在第四个化疗周期使用RECIST 1.1标准进行评估：研究结果显示，受试者的基因型存在差异，频率分布如下：AA基因型（82.9%）、AC基因型（15.9%）和CC基因型（1.2%）。ERCC2 rs13181 CC + AC 与 AA 与 RECIST 1.1 的相关性分析得出的几率比（OR）为 1.042（95% CI：0.292- 3.715；P=0.950）。将癌症分期和化疗方案作为附加变量进行多变量分析后，调整后的几率比（aOR）为0.970（95% CI：0.263- 3.568；P=0.963）：本研究未发现ERCC2 rs13181多态性与化疗反应之间存在统计学意义上的显著关联。然而，这项研究强调了印尼人群中存在遗传变异，其中 AA 基因型最为普遍，这可能会影响化疗反应。研究结果提供了初步数据，为今后开展全面的队列观察研究奠定了基础：ERCC2、基因多态性、印度尼西亚、RECIST 1.1、铂类药物

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.